Lins Stephan, Kim Ryong, Krüger Lars, Chrzanowska Krystyna H, Seemanova Eva, Digweed Martin
Institut für Humangenetik, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany.
Gene. 2009 Nov 1;447(1):12-7. doi: 10.1016/j.gene.2009.07.013. Epub 2009 Jul 25.
Patients affected by the autosomal recessive Nijmegen Breakage Syndrome (NBS [MIM 251260]) have possibly the highest risk for developing a malignancy of all the chromosomal instability syndromes. This reflects the profound disturbance to genomic integrity and cellular homeostasis that is caused by the mutation of the essential mammalian gene, NBN. Whilst null-mutation of Nbn is lethal in the mouse, NBS patients survive due to the fact that the common human founder mutation, found in over 90% of patients, is in fact hypomorphic and leads, by alternative translation, to varying amounts of a partially functional carboxy-terminal protein fragment, p70-nibrin. The expression level of p70-nibrin correlates with cancer incidence amongst patients. Using real-time PCR we have now found that the variation in p70-nibrin expression cannot be attributed to differences in mRNA quantity and that nonsense-mediated mRNA decay is not responsible for the observed variation. We discuss an alternative explanation for p70-nibrin expression variation.
患有常染色体隐性尼曼-匹克氏症候群（NBS [MIM 251260]）的患者，在所有染色体不稳定症候群中，可能具有罹患恶性肿瘤的最高风险。这反映出由关键的哺乳动物基因NBN突变所导致的对基因组完整性和细胞稳态的严重干扰。虽然Nbn的无效突变在小鼠中是致命的，但NBS患者能够存活，原因是在超过90%的患者中发现的常见人类始祖突变实际上是亚效等位基因，通过可变剪接产生不同数量的部分功能性羧基末端蛋白片段p70-尼布林。p70-尼布林的表达水平与患者中的癌症发病率相关。通过实时聚合酶链反应，我们现在发现p70-尼布林表达的变化不能归因于mRNA数量的差异，并且无义介导的mRNA降解也不是观察到的变化的原因。我们讨论了p70-尼布林表达变化的另一种解释。
